1. Field of the Invention
The invention relates generally to screening assays, and more specifically to methods of identifying agents that can modulate the expression and/or activity of an acyl homoserine lactone (AHL) acylase that breaks down long chain AHLs, but not short chain AHLs, in γ-proteobacteria such as Pseudomonas aeruginosa, to agents identified by such methods, and to methods of using the agents to treat a γ-proteobacteria infection by inhibiting quorum sensing activity by the bacteria.
2. Background Information
Pseudomonas aeruginosa, an opportunistic pathogen, is a gram-negative γ-proteobacteria. P. aeruginosa can thrive in a variety of environments, requiring only minimal nutrients and moisture. For example, P. aeruginosa exists in soil, water, and on animals. P. aeruginosa releases enzymes such as an elastase, an alkaline protease, and a cytotoxin that aid in the invasion and destruction of host tissues. In an infected host, P. aeruginosa often invades small arteries and veins, which frequently leads to metastatic nodular lesions in the lungs. Pseudomonas infections can be aggressive, often result in sepsis, and are associated with a high mortality rate.
Immunocompromised individuals such as patients with burns, urinary tract infections, or cystic fibrosis are particularly susceptible to Pseudomonas infections. In cystic fibrosis patients, for example, pneumonia due to P. aeruginosa infection is common, likely due to accumulated bronchial secretions providing an environment in which the Pseudomonas can flourish. Further, P. aeruginosa is extremely resistant to antibiotics and, therefore, treatment must be aggressive and, nevertheless, is often unsuccessful. Thus, a need exists for drugs that can be used to successfully treat Pseudomonas infections. The present invention satisfies this need, and provides additional advantages.